Fas-associated factor 1 and Parkinson's disease

Ranjita Betarbet; Leah R. Anderson; Marla Gearing; Tiffany R. Hodges; Jason J. Fritz; James J. Lah; Allan I. Levey

Neurobiology of Disease (Sep 2008)

Fas-associated factor 1 and Parkinson's disease

Ranjita Betarbet,
Leah R. Anderson,
Marla Gearing,
Tiffany R. Hodges,
Jason J. Fritz,
James J. Lah,
Allan I. Levey

Affiliations

Ranjita Betarbet: Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505G, 615 Michael Street, Atlanta, Georgia 30322, USA; Department of Neurology, Emory University, Atlanta, Georgia 30322, USA; Corresponding author. Fax: +1 404 727 3728.
Leah R. Anderson: Center for Science Education, Emory University, Atlanta, Georgia 30322, USA
Marla Gearing: Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505G, 615 Michael Street, Atlanta, Georgia 30322, USA; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA
Tiffany R. Hodges: School of Medicine, Duke University Medical Center, Durham, NC 27710, USA
Jason J. Fritz: Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505G, 615 Michael Street, Atlanta, Georgia 30322, USA; Department of Neurology, Emory University, Atlanta, Georgia 30322, USA
James J. Lah: Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505G, 615 Michael Street, Atlanta, Georgia 30322, USA; Department of Neurology, Emory University, Atlanta, Georgia 30322, USA
Allan I. Levey: Center for Neurodegenerative Disease, Emory University, Whitehead Biomedical Research Building, Room 505G, 615 Michael Street, Atlanta, Georgia 30322, USA; Department of Neurology, Emory University, Atlanta, Georgia 30322, USA

Journal volume & issue: Vol. 31, no. 3
pp. 309 – 315

Abstract

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Fas-associated factor 1 or FAF1 is a Fas-binding protein implicated in apoptosis. FAF1 is the product of a gene at PARK 10 locus on chromosome 1p32, a locus associated with late-onset PD [Hicks, A.A., Petursson, H., Jonsson, T., Stefansson, H., Johannsdottir, H.S., Sainz, J., Frigge, M.L.et al., 2002. A susceptibility gene for late-onset idiopathic Parkinson's disease. Ann Neurol. 52, 549–555.]. In the present study we investigated the role of FAF1 in cell death and in Parkinson's disease (PD) pathogenesis. FAF1 levels were significantly increased in frontal cortex of PD as well as in PD cases with Alzheimer's disease (AD) pathology compared to control cases. Changes in FAF1 expression were specific to PD-related α-synuclein pathology and nigral cell loss. In addition, PD-related insults including, mitochondrial complex I inhibition, oxidative stress, and increased α-synuclein expression specifically increased endogenous FAF1 expression in vitro. Increased FAF1 levels induced cell death and significantly potentiated toxic effects of PD-related stressors including, oxidative stress, mitochondrial complex I inhibition and proteasomal inhibition. These studies, together with previous genetic linkage studies, highlight the potential significance of FAF1 in pathogenesis of idiopathic PD.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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